Community-engaged basic science in an NCI-designated comprehensive cancer center: antioxidants and chemotherapeutic efficacy.

PURPOSE: While community engagement has been a longstanding aspect of cancer-relevant research in social and behavioral sciences, it is far less common in basic/translational/clinical research. With the National Cancer Institute's incorporation of Community Outreach and Engagement into the Cancer Center Support Grant guidelines, successful models are desirable. We report on a pilot study supported by the University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC), that used a community-engaged, data-driven process to inform a pre-clinical study of the impact of antioxidants on the efficacy of platinum-based chemotherapeutics. METHODS: We conducted a survey of UMGCCC catchment area residents (n = 120) to identify commonly used antioxidants. We then evaluated the effect of individually combining commonly used antioxidants from the survey (vitamin C, green tea, and melatonin) with platinum agents in models of non-small cell lung cancer (A549), colon adenocarcinoma (SW620) and head and neck squamous cell carcinoma (FaDu). RESULTS: In vitro, the anti-neoplastic activity of each chemotherapy was not potentiated by any of the antioxidants. Instead, when combined at fixed ratios, most antioxidant-chemotherapy combinations were antagonistic. In vivo, addition of antioxidants did not improve chemotherapeutic efficacy and in a FaDu-tumor bearing model, cisplatin-mediated tumor growth inhibition was significantly impeded by the addition of epigallocatechin gallate, the main antioxidant in green tea. CONCLUSION: These initial findings do not support addition of antioxidant supplementation to improve platinum-based chemotherapeutic efficacy. This study's approach can serve as a model of how to bring together the two seemingly discordant areas of basic research and community engagement.

Accuracy of National Surgical Quality Improvement Program Risk Calculator Among Elderly Patients Undergoing Pancreas Resection.

INTRODUCTION: A preoperative goals-of-care discussion is essential in maintaining the autonomy of older adults who require surgery. The purpose of this study was to determine the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) risk calculator and its association with age for patients who underwent pancreatectomy. METHODS: Using the American College of Surgeons NSQIP database, patients who underwent pancreatectomy between 2012 and 2015 were identified. Age was categorized into three groups: 18-64, 65-79, and 80-89 y. Analysis of variance and Pearson correlation coefficients were employed to assess differences between age categories in predicted and actual mortality and morbidity. Covariate-adjusted logistic regression models were employed to evaluate associations while accounting for potential confounders. RESULTS: A total of 17,906 patients were included. The correlation between actual and predicted mortality was low (r = 0.14, P < 0.001). This correlation was weakest for the age category 80-89 y (r = 0.04, P = 0.07) and strongest for 65-79 y category (r = 0.14, P > 0.001). The correlation was weakest among patients who underwent pancreatoduodenectomy (r = 0.06, P = 0.08) and in this group mortality was overestimated for older adults in the age group 80-89 (actual mortality: 3.2% versus predicted mortality: 5.6%, P = 0.08). After adjusting for covariates, the interaction term between age and predicted mortality (P = 0.0021) indicated that the relationship between predicted and actual mortality is significantly influenced by patient age. CONCLUSIONS: The NSQIP risk calculator appears to overestimate mortality and morbidity risk for elderly patients undergoing pancreatoduodenectomy. These predictions should be used with caution in preoperative goals-of-care discussions with patients aged 80 y and older.

Metformin use and the risk of anal intraepithelial neoplasia in type II diabetic patients.

AIM: Emerging evidence has suggested that metformin may be protective against the development of human-papillomavirus-related cancers. Anal intraepithelial neoplasia (AIN) is highly associated with human papillomavirus infection and a precancerous status of anal cancer. The aim of this study was to investigate the relationship between metformin usage and the development of AIN in a large national sample. METHODOLOGY: The IBM MarketScan dataset was used to design a nested case-control study from 2010 to 2017. Patients aged 18-65 years with type 2 diabetes mellitus (DM) were evaluated, and cases of AIN were identified. Four controls were randomly selected in the risk set of each case by using incidence density sampling. The association between metformin usage and AIN was assessed using multivariate logistic regression modelling. RESULTS: A total of 258 patients with type 2 DM were diagnosed with AIN during the study interval, and these were matched to 1032 control patients without a diagnosis of AIN. Patients who developed AIN had 38% lower odds of prior metformin use compared to those without a history of AIN (P < 0.01) and this finding remained robust after adjusting for age, sex, human immunodeficiency virus infection and DM complications (P = 0.02). Patients with AIN had 56% lower odds of long-term metformin use compared to control patients (P = 0.01). CONCLUSIONS: An AIN diagnosis in patients with DM is associated with 56% lower likelihood of prior metformin use. This relationship suggests that metformin could potentially play a protective role against AIN. Prospective studies in non-diabetic patients are warranted to examine these findings further.

The addition of spices and herbs to vegetables in the National School Lunch Program increased vegetable intake at an urban, economically-underserved, and predominantly African-American high school.

Vegetable intake is far below recommendations among African-American adolescents living in economically-underserved urban areas. While the National School Lunch Program (NSLP) helps overcome access barriers, vegetable intake remains challenging and novel interventions are required. A two-year, multi-phase, school-based intervention was conducted at an urban, economically-underserved, and predominantly African-American high school in Baltimore, Maryland to determine whether stakeholder-informed addition of spices and herbs to NSLP vegetables would increase intake. The stakeholder engagement phase included assessment of NSLP vegetable attitudes/preferences among 43 school stakeholders and subsequent student sensory testing. The second phase was conducted in the school cafeteria and consisted of eight weeks comparing student intake of typical vegetable recipes versus otherwise-identical recipes with spices and herbs. 4,570 student lunch plates were included in the vegetable intake comparison. Vegetable intake was measured by lunch tray plate waste. Willingness to try vegetables was assessed by the difference between plate waste and estimated mean vegetable served weight. Intake of typical vegetable recipes and vegetable recipes with spices and herbs was compared with student's t-test. Chi-square test was used to compare willingness to try vegetables. Total vegetable intake was 18.2% higher (8.22 grams per meal, p<0.0001) with spices and herbs than with typical recipes. There were no differences in trying vegetables with spices and herbs, although student-led advocacy was associated with increased trying vegetables with spices and herbs (78.8% with advocacy, 67.5% without advocacy, p<0.0001). The addition of spices and herbs to vegetables in the NSLP was feasible and associated with small increases in vegetable intake at an urban, economically-underserved, and predominantly African-American high school.

Preoperative Nutritional Status Predicts Major Morbidity After Primary Rectal Cancer Resection.

BACKGROUND: Malnutrition has been associated with adverse surgical outcomes, but data regarding its impact specifically in rectal cancer are sparse. The goal of this study was to use national data to determine the effects of malnutrition on surgical outcomes in rectal cancer resection. METHODS: Data were obtained from the American College of Surgeons National Surgical Quality Initiative Program from the years 2012-2015. Patients were included on the basis of International Classification of Disease 9/10 and Current Procedural Terminology codes for rectal cancer and proctectomy. Malnutrition was defined as body mass index <18.5 kg/m2, weight loss >10% in 6 mo, or preoperative albumin <3.5 mg/dL. Associations between malnutrition and postoperative outcomes were assessed by the Student t-test and chi-square test. Multivariate regression models were constructed to adjust for potential confounders of the association between malnutrition and surgical outcomes. RESULTS: Of the 9289 patients with primary rectal cancer who underwent resection, 1425 (15%) were in a state of malnutrition at the time of surgery. Patients with malnutrition had longer mean length of stay (LOS), and higher rates of 30-d mortality, wound infection, organ-space infection, sepsis, reoperation, prolonged LOS (>30 d), failure to wean off ventilator, renal failure, and cardiac arrest. With the exception of LOS, renal failure, and organ-space infection, malnutrition was still significantly associated with higher rates of these adverse outcomes after adjustment for confounders in multivariate regression models. CONCLUSIONS: Malnutrition is a practical marker associated with a variety of adverse outcomes after rectal cancer surgery, and it represents a potential target for nutritional therapies to improve surgical outcomes.

A Food-Derived Dietary Supplement Containing a Low Dose of Iron Improved Markers of Iron Status Among Nonanemic Iron-Deficient Women.

OBJECTIVE: Iron deficiency is the most common nutrient deficiency in the world. While deficiency can often be resolved through dietary supplementation with iron, adverse events are common and frequently preclude compliance. The objective of this study was to determine whether a food-derived dietary supplement containing a low dose of iron and nutrients that increase iron absorption could resolve iron deficiency with fewer adverse events than reported at higher doses. METHODS: A pilot clinical trial (NCT02683369) was conducted among premenopausal women with nonanemic iron deficiency that was verified by blood screening. Participants consumed a dietary supplement (Blood Builder®/Iron Response®) once daily for 8 weeks containing 26 mg of iron, vitamin C, folate, and other food-derived nutrients. Primary outcomes were markers of iron status (serum ferritin, hemoglobin, soluble transferrin receptor, total body iron stores) and secondary outcomes were self-reported fatigue and energy. All outcomes were assessed at baseline and 8 weeks. Adverse events were monitored with questionnaires, daily diaries, and contact with a physician. Dependent samples t test and Wilcoxon signed-rank test were used to analyze outcomes. RESULTS: Twenty-three participants enrolled in the study. Iron deficiency was resolved in the sample (mean serum ferritin: baseline = 13.9 µg/L, 8 weeks = 21.1 µg/L, p < 0.001). All other markers of iron status, fatigue, and energy also improved during the study (p < 0.04). No adverse events were reported. CONCLUSIONS: While larger and controlled studies are needed to confirm these findings, a food-derived dietary supplement with a low dose of iron and absorption-enhancing nutrients resolved iron deficiency and improved all other markers of iron status without any adverse events.

Yoga treatment for chronic non-specific low back pain.

BACKGROUND: Non-specific low back pain is a common, potentially disabling condition usually treated with self-care and non-prescription medication. For chronic low back pain, current guidelines state that exercise therapy may be beneficial. Yoga is a mind-body exercise sometimes used for non-specific low back pain. OBJECTIVES: To assess the effects of yoga for treating chronic non-specific low back pain, compared to no specific treatment, a minimal intervention (e.g. education), or another active treatment, with a focus on pain, function, and adverse events. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases and four trials registers to 11 March 2016 without restriction of language or publication status. We screened reference lists and contacted experts in the field to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials of yoga treatment in people with chronic non-specific low back pain. We included studies comparing yoga to any other intervention or to no intervention. We also included studies comparing yoga as an adjunct to other therapies, versus those other therapies alone. DATA COLLECTION AND ANALYSIS: Two authors independently screened and selected studies, extracted outcome data, and assessed risk of bias. We contacted study authors to obtain missing or unclear information. We evaluated the overall certainty of evidence using the GRADE approach. MAIN RESULTS: We included 12 trials (1080 participants) carried out in the USA (seven trials), India (three trials), and the UK (two trials). Studies were unfunded (one trial), funded by a yoga institution (one trial), funded by non-profit or government sources (seven trials), or did not report on funding (three trials). Most trials used Iyengar, Hatha, or Viniyoga forms of yoga. The trials compared yoga to no intervention or a non-exercise intervention such as education (seven trials), an exercise intervention (three trials), or both exercise and non-exercise interventions (two trials). All trials were at high risk of performance and detection bias because participants and providers were not blinded to treatment assignment, and outcomes were self-assessed. Therefore, we downgraded all outcomes to 'moderate' certainty evidence because of risk of bias, and when there was additional serious risk of bias, unexplained heterogeneity between studies, or the analyses were imprecise, we downgraded the certainty of the evidence further.For yoga compared to non-exercise controls (9 trials; 810 participants), there was low-certainty evidence that yoga produced small to moderate improvements in back-related function at three to four months (standardized mean difference (SMD) -0.40, 95% confidence interval (CI) -0.66 to -0.14; corresponding to a change in the Roland-Morris Disability Questionnaire of mean difference (MD) -2.18, 95% -3.60 to -0.76), moderate-certainty evidence for small to moderate improvements at six months (SMD -0.44, 95% CI -0.66 to -0.22; corresponding to a change in the Roland-Morris Disability Questionnaire of MD -2.15, 95% -3.23 to -1.08), and low-certainty evidence for small improvements at 12 months (SMD -0.26, 95% CI -0.46 to -0.05; corresponding to a change in the Roland-Morris Disability Questionnaire of MD -1.36, 95% -2.41 to -0.26). On a 0-100 scale there was very low- to moderate-certainty evidence that yoga was slightly better for pain at three to four months (MD -4.55, 95% CI -7.04 to -2.06), six months (MD -7.81, 95% CI -13.37 to -2.25), and 12 months (MD -5.40, 95% CI -14.50 to -3.70), however we pre-defined clinically significant changes in pain as 15 points or greater and this threshold was not met. Based on information from six trials, there was moderate-certainty evidence that the risk of adverse events, primarily increased back pain, was higher in yoga than in non-exercise controls (risk difference (RD) 5%, 95% CI 2% to 8%).For yoga compared to non-yoga exercise controls (4 trials; 394 participants), there was very-low-certainty evidence for little or no difference in back-related function at three months (SMD -0.22, 95% CI -0.65 to 0.20; corresponding to a change in the Roland-Morris Disability Questionnaire of MD -0.99, 95% -2.87 to 0.90) and six months (SMD -0.20, 95% CI -0.59 to 0.19; corresponding to a change in the Roland-Morris Disability Questionnaire of MD -0.90, 95% -2.61 to 0.81), and no information on back-related function after six months. There was very low-certainty evidence for lower pain on a 0-100 scale at seven months (MD -20.40, 95% CI -25.48 to -15.32), and no information on pain at three months or after seven months. Based on information from three trials, there was low-certainty evidence for no difference in the risk of adverse events between yoga and non-yoga exercise controls (RD 1%, 95% CI -4% to 6%).For yoga added to exercise compared to exercise alone (1 trial; 24 participants), there was very-low-certainty evidence for little or no difference at 10 weeks in back-related function (SMD -0.60, 95% CI -1.42 to 0.22; corresponding to a change in the Oswestry Disability Index of MD -17.05, 95% -22.96 to 11.14) or pain on a 0-100 scale (MD -3.20, 95% CI -13.76 to 7.36). There was no information on outcomes at other time points. There was no information on adverse events.Studies provided limited evidence on risk of clinical improvement, measures of quality of life, and depression. There was no evidence on work-related disability. AUTHORS' CONCLUSIONS: There is low- to moderate-certainty evidence that yoga compared to non-exercise controls results in small to moderate improvements in back-related function at three and six months. Yoga may also be slightly more effective for pain at three and six months, however the effect size did not meet predefined levels of minimum clinical importance. It is uncertain whether there is any difference between yoga and other exercise for back-related function or pain, or whether yoga added to exercise is more effective than exercise alone. Yoga is associated with more adverse events than non-exercise controls, but may have the same risk of adverse events as other back-focused exercise. Yoga is not associated with serious adverse events. There is a need for additional high-quality research to improve confidence in estimates of effect, to evaluate long-term outcomes, and to provide additional information on comparisons between yoga and other exercise for chronic non-specific low back pain.

Evaluation of the Balanced Menus Challenge: a healthy food and sustainability programme in hospitals in Maryland.

OBJECTIVE: The Balanced Menus Challenge (BMC) is a national effort to bring the healthiest, most sustainably produced meat available into health-care settings to preserve antibiotic effectiveness and promote good nutrition. The present study evaluated the outcomes of the BMC in the Maryland/Washington, DC region. DESIGN: The BMC is a cost-effective programme whereby participating hospitals reduce meat purchases by 20 % of their budget, then invest the savings into purchasing sustainably produced meat. A mixed-methods retrospective assessment was conducted to assess (i) utilization of the BMC 'implementation toolkit' and (ii) achievement of the 20 % reduction in meat purchases. Previous survey data were reviewed and semi-structured interviews were conducted. SETTING: Hospitals located in the Maryland/Washington, DC region, USA, that adopted the BMC. SUBJECTS: Twelve hospitals signed the BMC in the Maryland/Washington, DC region and six were available for interview. RESULTS: Three hospitals in the Maryland/Washington, DC region that signed the BMC tracked their progress and two achieved a reduction in meat procurement by ≥20 %. One hospital demonstrated that the final outcome goal of switching to a local and sustainable source for meat is possible to achieve, at least for a portion of the meal budget. The three hospitals that reduced meat purchases also received and used the highest number of BMC implementation tools. There was a positive correlation between receipt and usage of implementation tools (r=0·93, P=0·005). CONCLUSIONS: The study demonstrates that hospitals in the Maryland/Washington, DC region that sign the BMC can increase the amount of sustainably produced meat purchased and served.

Soy foods and supplementation: a review of commonly perceived health benefits and risks.

In recent years, the impact of soy foods and supplements upon human health has become increasingly controversial among the general public. No one has conducted a broad evaluation of the scientific evidence supporting or refuting popular perceptions of the health effects of soy consumption. In this article, the authors have conducted a comprehensive assessment of the literature surrounding the health effects of soy consumption that are of greatest interest. This review has focused on 5 health benefits- relief of menopausal symptoms and prevention of heart disease, breast cancer, prostate cancer, and osteoporosis, and 5 health risks-increased risk of breast cancer, male hormonal and fertility problems, hypothyroidism, antinutrient content, and harmful processing by-products. Systematic reviews of human trials, prospective human trials, observational human studies, animal models, in vitro studies, and laboratory analyses of soy components were included for review. This literature review revealed that soy foods and isoflavones may provide relief from menopausal symptoms and protect against breast cancer and heart disease. Soy does not appear to offer protection against osteoporosis. The evidence on male fertility and reproductive hormones was conflicting; some studies demonstrated a deleterious impact caused by soy consumption and others showed no effect. Soy supplementation also appears to affect thyroid function in an inconsistent manner, as studies have shown both increases and decreases in the same parameters of thyroid activity. Soaking, fermentation, and heating may reduce problematic antinutrients contained in soy. The authors found that consuming moderate amounts of traditionally prepared and minimally processed soy foods may offer modest health benefits while minimizing potential for adverse health effects. However, additional studies are necessary to elucidate the variable thyroid response to soy supplementation, and more rigorous studies are required to assess dose-response relationships, the relationship between intestinal-flora composition and the response to soy, potential fertility issues among males, and the unknown long-term health effects of consuming highly processed modern soy foods.

"Food faddists and pseudoscientists!": Reflections on the history of resistance to ultra-processed foods.

The term 'ultra-processed food' emerged in the 1980s, mostly used in reference to highly-processed convenience foods and snacks, often energy-dense, poor in nutrients, and inclusive of various synthetic additives such as emulsifiers, colors, artificial sweeteners, and/or flavor enhancers. Concern over such foods was part of the growing holistic and environmental health movements of the 1970-80s; yet, those who raised alarm about the encroachment of ultra-processed foods were often labeled, especially by industry and their powerful allies, as 'food faddists' and 'pseudoscientists'. Today, the topic of ultra-processed foods is generating massive personal, public, and planetary health interest. However, other than discussing the history of the NOVA food classification system, a useful tool that has allowed researchers to more accurately separate foods based on processing, most lay media and academic articles are ahistorical. That is, there is a tendency to present the term ultra-processed food(s) as a relatively new entrance into the lexicon, and by default, the idea that health-related pushback on ultra-processed foods is a relatively new phenomenon. This omission overlooks decades of determined advocacy and clinical work, much of it by pioneers within the holistic medicine (now integrative, functional, and lifestyle medicine) movement. Here in this reflection paper, the authors will use historical research and reporting to fill in the historical gap and articulate the saliency of why it matters.

The Safety and Comparative Effectiveness of Non-Psychoactive Cannabinoid Formulations for the Improvement of Sleep: A Double-Blinded, Randomized Controlled Trial.

BACKGROUND: Clinical evidence on the use of cannabidiol (CBD) for sleep remains limited. Even fewer studies have tested the comparative effectiveness of cannabinoid formulations found within CBD products used for sleep or how they compare to other complementary therapies such as melatonin. METHODS: Participants (N = 1,793 adults experiencing symptoms of sleep disturbance) were randomly assigned to receive a 4-week supply of 1 of 6 products (all capsules) containing either 15 mg CBD or 5 mg melatonin, alone or in combination with minor cannabinoids. Sleep disturbance was assessed over a period of 5 weeks (baseline week and 4 weeks of product use) using Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A, administered via weekly online surveys. A linear mixed-effects regression model was used to assess the differences in the change in sleep disturbance through time between each active product arm and CBD isolate. RESULTS: All formulations exhibited a favorable safety profile (12% of participants reported a side effect and none were severe) and led to significant improvements in sleep disturbance (p < 0.001 in within-group comparisons). Most participants (56% to 75%) across all formulations experienced a clinically important improvement in their sleep quality. There were no significant differences in effect, however, between 15 mg CBD isolate and formulations containing 15 mg CBD and 15 mg cannabinol (CBN), alone or in combination with 5 mg cannabichromene (CBC). There were also no significant differences in effect between 15 mg CBD isolate and formulations containing 5 mg melatonin, alone or in combination with 15 mg CBD and 15 mg CBN. CONCLUSIONS: Our findings suggest that chronic use of a low dose of CBD is safe and could improve sleep quality, though these effects do not exceed that of 5 mg melatonin. Moreover, the addition of low doses of CBN and CBC may not improve the effect of formulations containing CBD or melatonin isolate.

Functional medicine health coaching improved elimination diet compliance and patient-reported health outcomes: Results from a randomized controlled trial.

BACKGROUND: The objective of this study was to determine whether an elimination diet with virtually provided functional medicine health coaching support would be more effective than a typical self-guided elimination diet with respect to dietary compliance and patient-reported health and quality of life. METHODS: A parallel arm, randomized controlled trial was conducted among a sample of healthcare professionals. Participants were randomized to either an elimination diet with 5 sessions of functional medicine health coaching support (intervention arm) or a self-guided elimination diet (control arm). Outcomes assessed at baseline and at the conclusion of the 10-week study included PROMIS Global Health (GH) and medical symptoms questionnaire (MSQ). Compliance with the elimination diet was assessed at the conclusion of the study. Baseline and end of study outcomes were compared within study arms via paired t tests and between study arms with unpaired t tests. Subgroup analysis of symptomatology at baseline was performed. RESULTS: 125 randomized participants (n = 64 intervention, n = 61 control) provided baseline outcomes data. There were statistically and clinically significant within-group improvements in patient-reported outcomes in both the intervention arm (PROMIS GH-physical = 4.68, PROMIS GH-mental = 3.53, MSQ = 28.9) and control arm (PROMIS GH-physical = 48.4, PROMIS GH-mental = 3.18, MSQ = 24.1). There were no between-group differences in the primary analysis (P > .1). However, participants with more symptoms at baseline had statistically and clinically significant between-group differences in PROMIS GH-mental health (3.90, P = .0038) and MSQ (12.3, P = .047) scores that favored the functional medicine health coaching arm. CONCLUSIONS: An elimination diet, whether self-guided or with functional medicine health coaching support, may improve patient-reported health outcomes among relatively healthy healthcare professionals. While studies in more diverse samples are needed, functional medicine health coaching support appears to be superior to a self-guided approach with regard to both dietary compliance and improving health outcomes among those with greater symptomatology.

Adjuvant chemotherapy in stage 1 colon cancer: Patient characteristics and survival analysis from the national cancer database.

BACKGROUND: A subset of patients in ACS-NCDB with stage-1 colon cancer received adjuvant chemotherapy (AC), in contrast to national guidelines. This study aimed to define this population and evaluate associations between AC and survival. METHODS: Patients with T1-2N0 colon cancer from 2004 to 2016 were separated into AC and non-AC groups. Adverse pathological features (APF) included T2, poor differentiation, lymphovascular invasion, positive margin, and inadequate lymph nodes (<12). Cox proportional hazard models were used to estimate prognostic factors for overall survival (OS). RESULTS: A total of 1745 of 139,857 patients (1.2 %) received AC. Receiving AC was associated with male sex (p = 0.02), uninsured (p < 0.01), low income (p = 0.02), or having ≥2 APFs (p < 0.001). In the total cohort, AC was associated with increased mortality (HR 1.14 [1.04-1.24] P < 0.01). On subset analysis, AC was associated with improved OS for patients with ≥2 APFs (log-rank P=<0.001), and decreased mortality when adjusted for covariates (HR 0.81 [0.69-0.95] P=<0.01). The most significant predictor of mortality was old age (HR 3.78 [3.67, 3.89] p ≤ 0.01), followed by higher Charlson Comorbidity Index (HR 1.73 [1.69, 1.76] (p ≤ 0.01), and higher APF score (HR 1.46 [1.42, 15.2] p ≤ 0.01). CONCLUSION: AC was associated with decreased survival in the total cohort of stage 1 colon cancer patients, but was associated with improved survival for patients with multiple APFs.

Reversal of Autism Symptoms among Dizygotic Twins through a Personalized Lifestyle and Environmental Modification Approach: A Case Report and Review of the Literature.

The prevalence of autism has been increasing at an alarming rate. Even accounting for the expansion of autism spectrum disorder diagnostic (ASD) criteria throughout the 1990's, there has been an over 300% increase in ASD prevalence since the year 2000. The often debilitating personal, familial, and societal sequelae of autism are generally believed to be lifelong. However, there have been several encouraging case reports demonstrating the reversal of autism diagnoses, with a therapeutic focus on addressing the environmental and modifiable lifestyle factors believed to be largely underlying the condition. This case report describes the reversal of autism symptoms among dizygotic, female twin toddlers and provides a review of related literature describing associations between modifiable lifestyle factors, environmental exposures, and various clinical approaches to treating autism. The twins were diagnosed with Level 3 severity ASD "requiring very substantial support" at approximately 20 months of age following concerns of limited verbal and non-verbal communication, repetitive behaviors, rigidity around transitions, and extensive gastrointestinal symptoms, among other common symptoms. A parent-driven, multidisciplinary, therapeutic intervention involving a variety of licensed clinicians focusing primarily on addressing environmental and modifiable lifestyle factors was personalized to each of the twin's symptoms, labs, and other outcome measures. Dramatic improvements were noted within several months in most domains of the twins' symptoms, which manifested in reductions of Autism Treatment Evaluation Checklist (ATEC) scores from 76 to 32 in one of the twins and from 43 to 4 in the other twin. The improvement in symptoms and ATEC scores has remained relatively stable for six months at last assessment. While prospective studies are required, this case offers further encouraging evidence of ASD reversal through a personalized, multidisciplinary approach focusing predominantly on addressing modifiable environmental and lifestyle risk factors.

Nutritional Criminology: Why the Emerging Research on Ultra-Processed Food Matters to Health and Justice.

There is mounting concern over the potential harms associated with ultra-processed foods, including poor mental health and antisocial behavior. Cutting-edge research provides an enhanced understanding of biophysiological mechanisms, including microbiome pathways, and invites a historical reexamination of earlier work that investigated the relationship between nutrition and criminal behavior. Here, in this perspective article, we explore how this emergent research casts new light and greater significance on previous key observations. Despite expanding interest in the field dubbed 'nutritional psychiatry', there has been relatively little attention paid to its relevancy within criminology and the criminal justice system. Since public health practitioners, allied mental health professionals, and policymakers play key roles throughout criminal justice systems, a holistic perspective on both historical and emergent research is critical. While there are many questions to be resolved, the available evidence suggests that nutrition might be an underappreciated factor in prevention and treatment along the criminal justice spectrum. The intersection of nutrition and biopsychosocial health requires transdisciplinary discussions of power structures, industry influence, and marketing issues associated with widespread food and social inequalities. Some of these discussions are already occurring under the banner of 'food crime'. Given the vast societal implications, it is our contention that the subject of nutrition in the multidisciplinary field of criminology-referred to here as nutritional criminology-deserves increased scrutiny. Through combining historical findings and cutting-edge research, we aim to increase awareness of this topic among the broad readership of the journal, with the hopes of generating new hypotheses and collaborations.

Linoleic Acid: A Narrative Review of the Effects of Increased Intake in the Standard American Diet and Associations with Chronic Disease.

The intake of linoleic acid (LA) has increased dramatically in the standard American diet. LA is generally promoted as supporting human health, but there exists controversy regarding whether the amount of LA currently consumed in the standard American diet supports human health. The goal of this narrative review is to explore the mechanisms that underlie the hypothesis that excessive LA intake may harm human health. While LA is considered to be an essential fatty acid and support health when consumed in modest amounts, an excessive intake of LA leads to the formation of oxidized linoleic acid metabolites (OXLAMs), impairments in mitochondrial function through suboptimal cardiolipin composition, and likely contributes to many chronic diseases that became an epidemic in the 20th century, and whose prevalence continues to increase. The standard American diet comprises 14 to 25 times more omega-6 fatty acids than omega-3 fatty acids, with the majority of omega-6 intake coming from LA. As LA consumption increases, the potential for OXLAM formation also increases. OXLAMs have been associated with various illnesses, including cardiovascular disease, cancer, and Alzheimer's disease, among others. Lowering dietary LA intake can help reduce the production and accumulation of OXLAMs implicated in chronic diseases. While there are other problematic components in the standard American diet, the half-life of LA is approximately two years, which means the damage can be far more persistent than other dietary factors, and the impact of reducing excessive LA intake takes time. Therefore, additional research-evaluating approaches to reduce OXLAM formation and cardiolipin derangements following LA consumption are warranted.

Linear versus Turbulent Airflow Tracheostomy Heat and Moisture Exchangers: A Crossover Study.

OBJECTIVE: This study aimed to evaluate the impact of two tracheostomy heat and moisture exchangers (HMEs), namely the Shikani Oxygen HME™ (S-O2 HME, ball type, turbulent airflow) and Mallinckrodt Tracheolife II DAR HME (M-O2 HME; flapper type, linear airflow) on tracheobronchial mucosal health, oxygenation, humidification, and patient preference. METHODS: A randomized cross-over study was conducted with HME-naïve long-term tracheostomy subjects at two academic medical centers. Bronchoscopy assessments of mucosal health were performed at baseline and day 5 of HME application, along with oxygen saturation (SpO2 ) and breathed air humidity at four oxygen flow rates (1, 2, 3, and 5 lpm). Patient preference was assessed on study conclusion. RESULTS: Both HMEs were associated with improved mucosal inflammation and decreased mucus production (p < 0.0002), with greater improvements in the S-O2 HME group (p < 0.007). Both HMEs improved humidity concentration at each oxygen flow rate (p < 0.0001), without significant differences between groups. SpO2 was greater for the S-O2 HME versus the M-O2 HME across all measured oxygen flow rates (p = 0.003). At low oxygen flow rates (1 or 2 lpm), the SpO2 in the S-O2 HME group was similar to that of the M-O2 HME at higher oxygen flow rates (3 or 5 lpm; p = 0.6). Ninety percent of subjects preferred the S-O2 HME. CONCLUSION: Tracheostomy HME uses correlated with improved indicators of tracheobronchial mucosal health, humidity, and oxygenation. The S-O2 HME outperformed the M-O2 HME with respect to tracheobronchial inflammation, SpO2 , and patient preference. Regular HME use by tracheostomy patients is recommended to optimize pulmonary health. Newer ball-type speaking valve technology additionally allows concomitant HME and speaking valve application. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3422-3428, 2023.

The Founder: Dispositional Greed, Showbiz, and the Commercial Determinants of Health.

Marketing unhealthy products by multinational corporations has caused considerable harm to individual health, collective wellbeing, and environmental sustainability. This is a growing threat to all societies and a significant contributor to the rising global burden of non-communicable diseases and early mortality. While there is growing consideration of the commercial determinants of health, this is largely focused on the methods by which unhealthy products are marketed and disseminated, including efforts to manipulate policy. Little attention has been paid to the underlying psychological traits and worldviews that are driving corporate greed. Here, we consider the role of "dispositional greed" in the commercial determinants of health with a focus on the historical attitudes and culture in the ultra-processed food industry-exemplified by "The Founder" of the McDonald's franchise. We argue that greed and associated psychological constructs, such as social dominance orientation and collective narcissism, permeate the commercial determinants of health at a collective level. This includes how a culture of greed within organizations, and individual dispositional greed, can magnify and cluster at scale, perpetuated by social dominance orientation. We also consider the ways in which "showbiz" marketing specifically targets marginalized populations and vulnerable groups, including children-in ways that are justified, or even celebrated despite clear links to non-communicable diseases and increased mortality. Finally, we consider how greed and exploitative mindsets mirror cultural values and priorities, with trends for increasing collective narcissism at scale, recognizing that many of these attitudes are cultivated in early life. A healthier future will depend on navigating a path that balances material prosperity with physical and spiritual wellbeing. This will require cultural change that places higher value on kindness, reciprocity, and mutualistic values especially in early life, for more equitable flourishing.

Effects of S-Allylcysteine-Rich Garlic Extract and Dietary Inorganic Nitrate Formula on Blood Pressure and Salivary Nitric Oxide: An Open-Label Clinical Trial Among Hypertensive Subjects.

INTRODUCTION:  The conversion of dietary inorganic nitrate (NO3-) to nitric oxide (NO) is a non-canonical pathway that plays an important role in NO biology, especially under pathological conditions. Inorganic NO3- supplementation is a proven method for controlling mild hypertension. Recent reports have suggested that another gaseous transmitter, hydrogen sulfide (H2S), influences NO biosynthesis and metabolism. Here, data are presented from an open-label clinical trial examining the effect of an encapsulated formulation (Vascanox® HP) that combines dietary sources of inorganic NO3- and S-allylcysteine (SAC), a source of H2S from garlic, on NO bioavailability and blood pressure in subjects experiencing elevated blood pressure or mild hypertension. METHODS:  An open-label clinical trial was conducted among patients with hypertension. Participants took Vascanox® for four weeks. Blood pressure was measured at baseline, two weeks, and four weeks. Salivary nitrite (NO2-), a surrogate of NO bioavailability, and NO3- were assessed prior to and two, six, and 24 hours after dosing on the first day of the study and prior to and two hours after dosing at subsequent study visits using saliva NO test strips. Changes in study outcomes over time were evaluated via analysis of variance (ANOVA) and paired t-tests. RESULTS:  Twelve participants completed the clinical trial. Vascanox® HP decreased systolic blood pressure by ~11 mmHg (p < 0.001) at two weeks and persisted beyond four weeks with daily supplementation. It also decreased the diastolic blood pressure of hypertensive subjects but not normotensive ones. The magnitude of the decrease was 11 mmHg (p < 0.01) at four weeks of study. Measurements of salivary concentrations of NO2- revealed high peak levels (743 uM) at two hours post-administration and a slow decay to elevated levels (348 uM) at 24 hours. NO2- salivary concentrations, a surrogate biomarker of NO bioavailability, remained above baseline for the duration of the study. CONCLUSIONS:  Vascanox® HP was shown to be a safe, effective, quick-acting, and long-lasting dietary supplement for controlling mild hypertension.

Beyond Plants: The Ultra-Processing of Global Diets Is Harming the Health of People, Places, and Planet.

Global food systems are a central issue for personal and planetary health in the Anthropocene. One aspect of major concern is the dramatic global spread of ultra-processed convenience foods in the last 75 years, which is linked with the rising human burden of disease and growing sustainability and environmental health challenges. However, there are also calls to radically transform global food systems, from animal to plant-derived protein sources, which may have unintended consequences. Commercial entities have moved toward this "great plant transition" with vigor. Whether motivated by profit or genuine environmental concern, this effort has facilitated the emergence of novel ultra-processed "plant-based" commercial products devoid of nutrients and fiber, and sometimes inclusive of high sugar, industrial fats, and synthetic additives. These and other ingredients combined into "plant-based" foods are often assumed to be healthy and lower in calorie content. However, the available evidence indicates that many of these products can potentially compromise health at all scales-of people, places, and planet. In this viewpoint, we summarize and reflect on the evidence and discussions presented at the Nova Network planetary health meeting on the "Future of Food", which had a particular focus on the encroachment of ultra-processed foods into the global food supply, including the plant-sourced animal protein alternatives (and the collective of ingredients therein) that are finding their way into global fast-food chains. We contend that while there has been much uncritical media attention given to the environmental impact of protein and macronutrient sources-meat vs. novel soy/pea protein burgers, etc.-the impact of the heavy industrial processing on both human and environmental health is significant but often overlooked, including effects on cognition and mental health. This calls for a more nuanced discourse that considers these complexities and refocuses priorities and value systems towards mutualistic solutions, with co-benefits for individuals, local communities, and global ecology.